Muccioli Giulio G, Wouters Johan, Scriba Gerhard K E, Poppitz Wolfgang, Poupaert Jacques H, Lambert Didier M
Unité de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, Faculté de Médecine, Université catholique de Louvain, Avenue E. Mounier 73, UCL-CMFA 7340, B-1200 Bruxelles, Belgium.
J Med Chem. 2005 Nov 17;48(23):7486-90. doi: 10.1021/jm0503906.
New 1-benzhydryl-3-phenylurea derivatives and their 1-benzhydryl-3-phenylthiourea isosteres were synthesized and evaluated for their human CB1 and CB2 cannabinoid receptor affinity. These compounds proved to be selective CB1 cannabinoid receptor ligands, acting as inverse agonists in a [35S]-GTPgammaS assay. The affinity of 3,5,5'-triphenylimidazolidine-2,4-dione and 3,5,5'-triphenyl-2-thioxoimidazolidin-4-one derivatives, possessing the 1-benzhydryl-3-phenylurea and 1-benzhydryl-3-phenylthiourea moiety, respectively, was also evaluated. In conclusion, the 1-benzhydryl-3-phenylurea scaffold seems to be a new interesting template of CB1 cannabinoid receptor inverse agonists.
合成了新型1-二苯甲基-3-苯基脲衍生物及其1-二苯甲基-3-苯基硫脲类似物，并评估了它们对人CB1和CB2大麻素受体的亲和力。这些化合物被证明是选择性CB1大麻素受体配体，在[35S]-GTPγS试验中作为反向激动剂起作用。还评估了分别具有1-二苯甲基-3-苯基脲和1-二苯甲基-3-苯基硫脲部分的3,5,5'-三苯基咪唑烷-2,4-二酮和3,5,5'-三苯基-2-硫代咪唑烷-4-酮衍生物的亲和力。总之，1-二苯甲基-3-苯基脲支架似乎是CB1大麻素受体反向激动剂的一种新的有趣模板。
